Pemetrexed in the treatment of relapsed/refractory primary central nervous system lymphoma.

BACKGROUND: Despite initial treatment with high-dose methotrexate-based regimens, many patients with primary central nervous system lymphoma (PCNSL) relapse and die from their disease. No standard of care exists at progression or relapse, but chemotherapy and in some cases radiation are usually used. Pemetrexed is a multitargeted antifolate, similar to methotrexate, but with a broader spectrum of activity. Because methotrexate is an integral part of PCSNL treatment, the authors assessed the antitumor activity and safety of pemetrexed in recurrent PCNSL. METHODS: Patients with relapsed/refractory PCNSL were enrolled in this trial. Treatment consisted of pemetrexed 900 mg/m(2) given every 3 weeks with low-dose dexamethasone, folate, and B12 supplementation. Each cycle was 6 weeks, and follow-up imaging was done before each new cycle. Treatment was continued until complete remission, progression, or toxicity. RESULTS: Eleven patients were treated, with a median age of 69.8 years and Karnofsky performance status of 70%; 10 of 11 patients had failed prior high-dose methotrexate. The median number of pemetrexed cycles given was 5, with an associated overall response rate of 55% and disease control rate of 91%. The 6-month progression-free survival (PFS) was 45%, median PFS was 5.7 months, and median overall survival was 10.1 months. Toxicities were primarily hematologic and infectious. CONCLUSIONS: Pemetrexed has single-agent activity in relapsed/refractory PCNSL. Toxicities were seen likely because of the higher than standard dose used. Further investigation of this agent or other multitargeted antifolates in PCNSL is warranted to determine optimal dose and efficacy in a more homogeneous population.

Genomics of human intracranial aneurysm wall.

BACKGROUND AND PURPOSE: The pathogenesis of intracranial aneurysms (IAs) remains elusive. Most studies have focused on individual genes, or a few interrelated genes or products, at a time in human IA. However, a broad view of pathologic mechanisms has not been investigated by identifying pathogenic genes and their interaction in networks. Our study aimed to analyze global gene expression patterns in the IA wall. METHODS: To our knowledge, our group was the first to perform Illumina microarray analysis on human IA via comparison of aneurysm wall and superficial temporal artery tissues from 6 consecutive patients. We adopted stringent statistical criteria to the individual genes; genes with a false discovery rate <0.01 and >2-fold change were selected as differentially expressed. To identify the overrepresented biologic pathways with the differentially expressed genes, we performed hypergeometric testing of the genes selected by relaxed criteria of P<0.01 and fold change >1.5. RESULTS: There are 326 distinct differentially expressed genes between IA and superficial temporal artery tissues (>2-fold change) with a false discovery rate <0.01. Analysis of the Kyoto Encyclopedia of Genes and Genomes pathways revealed the most impacted functional pathways: focal adhesion, extracellular matrix receptor interaction, and cell communication. Analysis of the Gene Ontology also supported the involvement of another 2 potentially important pathways: inflammatory response and apoptosis. CONCLUSIONS: The differentially expressed genes in the aneurysm wall may shed light on aneurysm pathobiology and provide novel targets for therapeutic intervention. These data will help generate hypotheses for future studies.

Acute symptomatic cerebellar tonsillar herniation following intraoperative lumbar drainage.

Complications of tonsillar herniation associated with lumbar drainage have been reported in the literature. However, acutely symptomatic tonsillar herniation after intraoperative lumbar drainage is rare. The following case illustrates the risk associated with cerebrospinal fluid (CSF) drainage in the setting of tonsillar herniation. The use of lumbar drainage during cranial surgery is a common practice for reducing intracranial pressure and enhancing exposure, but is not without complications. In addition to the complications of the insertion procedure itself, the change in pressure gradient between the intracranial and the suboccipital compartments is of key importance. The authors present the case of a patient who underwent a subtemporal craniotomy for resection of mesial temporal cavernous malformation with intraoperative lumbar drainage. The patient had a preexisting, asymptomatic 4-mm Chiari malformation and progressive neurological deficits resulting from further cerebellar tonsillar herniation in the early postoperative period developed, which required a lumbar blood patch, decompressive suboccipital craniectomy, and C-1 laminectomy with duroplasty. After placement of the lumbar drain and subsequent CSF drainage, the change in CSF pressure gradient above and below the foramen magnum probably led to the herniation. Unfortunately, the patient has lasting neuropathic pain and cervical cord signal changes on MR images.

Posterior fossa arteriovenous malformations.

Arteriovenous malformations (AVMs) of the posterior fossa are complex neurovascular lesions that are less common than their supratentorial counterparts, accounting for < 15% of all AVMs. The majority of patients with these lesions present with intracranial hemorrhage, a factor that has been consistently shown to increase one's risk for subsequent bleeding. Studies have additionally shown a posterior fossa or deep AVM location to portend a more aggressive natural history. The authors reviewed the literature on posterior fossa AVMs, finding their annual rupture rates to be as high as 11.6%, an important factor that underscores the importance of aggressive treatment of lesions amenable to intervention as therapeutic options and results continue to improve.

Advances in the radiosurgical treatment of large inoperable arteriovenous malformations.

Radiosurgery has proven useful in the treatment of small arteriovenous malformations (AVMs) of the brain. However, the volume of healthy tissue irradiated around large lesions is rather significant, necessitating reduced radiation doses to avoid complications. As a consequence, this can produce poorer obliteration rates. Several strategies have been developed in the past decade to circumvent dose-volume problems with large AVMs, including repeated treatments as well as dose, and volume fractionation schemes. Although success on par with that achieved in lesions smaller than 3 ml remains elusive, improvements over the obliteration rate, the complication rate or both have been reported after conventional single-dose stereotactic radiosurgery (SRS). Radiosurgery with a marginal dose or peripheral dose < 15 Gy rarely obliterates AVMs, yet most lesions diminish in size posttreatment. Higher doses may then be reapplied to any residual nidi after an appropriate follow-up period. Volume fractionation divides AVMs into smaller segments to be treated on separate occasions. Doses > 15 Gy irradiate target volumes of only 5-15 ml, thereby minimizing the radiation delivered to the surrounding brain tissue. Fewer adverse radiological effects with the use of fractionated radiosurgery over standard radiosurgery have been reported. Advances in AVM localization, dose delivery, and dosimetry have revived interest in hypofractionated SRS. Investigators dispensing >or= 7 Gy per fraction minimum doses have achieved occlusion with an acceptable number of complications in 53-70% of patients. The extended latency period between treatment and occlusion, about 5 years for emerging techniques (such as salvage, staged volume, and hypofractionated radiotherapy), exposes the patient to the risk of hemorrhage during that period. Nevertheless, improvements in dose planning and target delineation will continue to improve the prognosis in patients harboring inoperable AVMs.

Retrograde suction decompression of giant paraclinoid aneurysms using a No. 7 French balloon-containing guide catheter. Technical note.

The treatment of large and giant paraclinoid carotid artery (CA) aneurysms often requires the use of suction decompression for safe and effective occlusion. Both open and endovascular suction decompression techniques have been described previously. In this article the authors describe a revised endovascular suction decompression technique that provides several advantages in the treatment of large and giant paraclinoid and CA aneurysms. A 51-year-old woman presented with a relatively brief history of progressive visual loss in the right eye, nonspecific headache, and an afferent pupillary defect. After angiography studies had been obtained, it was determined that she had a giant right paraclinoid internal CA aneurysm with a dome size of approximately 26 mm on the right and a neck diameter of 10 mm. A modified technique was performed in which suction decompression was used. With the aid of a No. 7 French Concentric balloon guide catheter (Concentric Medical, Inc., Mountain View, CA) and application of a temporary clip distal to the aneurysm, the aneurysm was trapped and decompressed using retrograde suction through the guide catheter when the balloon was inflated. After satisfactory placement of three permanent clips, an intraoperative angiogram obtained through the same guide catheter confirmed CA patency. The aneurysm was then punctured and aspirated, ensuring complete occlusion of the aneurysm sac and reconstruction of the parent vessel. The patient made an excellent recovery and did not suffer any complications. She did not experience worsening in her vision. This technical modification to endovascular suction decompression allows several potential advantages, including higher volume decompression and the ability to deliver endovascular devices to distal arterial locations.

Current updates in perioperative management of intracerebral hemorrhage.

Spontaneous ICH remains a formidable disease that continues to disable and kill the majority of its victims. Treatment of the disease continues to be controversial and without any proved success, such as improvement in the disease mortality or the resulting disability in survivors. Primary prevention is the most effective medical intervention. Nevertheless, as the population continues to age and patients remain undertreated for hypertension, the incidence of ICH likely will increase, resulting in significant socioeconomic impact on society in the coming years. It is imperative that more research be conducted to improve treatment and outcomes of patients who have ICH. Unlike ischemic stokes or other causes of hemorrhagic stroke, such as SAH, where major advancement of treatment has led to improved outcomes, the increased incidence of ICH has not been matched with any considerable improvement in treatment. This burden to improve therapeutic interventions for patients who have ICH should be shared by all neurosurgeons, stroke neurologists, and critical care physicians who care for these patients on a regular basis. It is hoped that early diagnosis and resuscitation, prevention of hematoma growth, selective surgery or minimally invasive clot evacuation, and judicious critical care and rehabilitation will combine to lessen the burden of this disease.

Ruptured traumatic vertebral artery pseudoaneurysm in a child treated with trapping and posterior inferior cerebellar artery reimplantation. Case report and review of the literature.

The authors present the case report of a pediatric patient with a ruptured traumatic pseudoaneurysm of the intracranial vertebral artery (VA) from which the posterior inferior cerebellar artery (PICA) emerged. After considering multiple therapeutic options, the patient was treated surgically by trapping of the aneurysm segment and direct reimplantation of the PICA distal to the rupture site. In addition to presenting this unique case, the authors discuss the treatment of VA pseudoaneurysms and the various techniques for PICA revascularization. A review of the literature on PICA reimplantation is provided as an adjunct in the treatment of complex VA aneurysms.

Late morphological progression of a dissecting basilar artery aneurysm after staged bilateral vertebral artery occlusion: case report.

BACKGROUND: The authors present a patient who experienced late (5-year follow-up) morphological progression of a dissecting aneurysm of the distal basilar artery after treatment with a combined microsurgical and neuroendovascular Hunterian strategy. In addition to postulating about the possible reasons underlying the evolution of this lesion, the role of stenting is discussed. CASE DESCRIPTION: The patient was 37 years old when she suffered a subarachnoid hemorrhage from spontaneous basilar artery dissection. At the time of the hemorrhage, minimal aneurysmal enlargement was noted angiographically, and she was therefore treated nonoperatively. On reimaging 5 months later, massive enlargement of the aneurysm was noted. The patient was treated with staged bilateral vertebral artery sacrifice using a combination of microsurgical and neuroendovascular techniques. The dominant vertebral artery was clip-ligated distal to the posteroinferior cerebellar artery, whereas the contralateral vertebral artery was coil-occluded cervically 1 week later. CONCLUSIONS: Despite the patient remaining asymptomatic, follow-up angiography 5 years after the initial hemorrhage revealed further enlargement of the aneurysm as well as a newly discovered inferiorly projecting daughter sac measuring 5 mm in diameter. Clearly, certain aneurysms exist for which indirect approaches involving hemodynamic attenuation fail to prevent progression. With greater refinements in stent technology, such lesions may be more effectively treated.

Update on current registries and trials of carotid artery angioplasty and stent placement.

Stroke remains the leading cause of disability in adults and the third leading cause of death in the US. Carotid artery (CA) occlusive disease is the primary pathophysiological source of 10 to 20% of all strokes. Carotid endarterectomy (CEA) has been shown to reduce the risk of stroke in patients with both symptomatic and asymptomatic extracranial CA stenosis. Carotid artery angioplasty and stent placement has recently emerged as an alternative to CEA for primary and secondary prevention of stroke related to CA stenosis. With the advent of the embolic protection device, the safety of CA angioplasty and stent placement has approached, if not surpassed, that of CEA. In particular, the former has come to be considered as a first-line therapy in the management of CA stenotic disease in individuals at high risk for complications related to surgical intervention. Preliminary data from multiple registries have demonstrated that CA angioplasty and stent placement is an effective means of treating CA stenosis. The results of the Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy trial have demonstrated that this modality has a significant role in the management of CA disease in symptomatic and asymptomatic patients with risk factors for high rates of surgery-related morbidity or mortality. With the completion of the Carotid Revascularization Endarterectomy versus Stent Trial, the role of CA angioplasty and stent placement in the prevention of stroke in all individuals with significant CA stenosis should be better demarcated. This treatment modality promises to assume a central role in stroke prophylaxis in patients with CA disease who are at high risk for complications related to surgery.

Microsurgical resection of infratentorial arteriovenous malformations.

Successful microsurgical resection of an infratentorial arteriovenous malformation (AVM) requires both surgical skill and intraoperative judgment. Extensive practical experience in treating these complex lesions, which is acquired over many years, is of substantial value during each new operation. The authors present the surgical approaches and techniques used for the treatment of posterior fossa AVMs based largely on the strategies acquired and developed by the senior author (H.H.B.). Emphasis is placed on conceptual principles of AVM excision, as well as principles incorporated for the treatment of each specific type of infratentorial malformation.

Extended lateral transsylvian approach for basilar bifurcation aneurysms.

The surgical management of aneurysms of the basilar apex is one of the most challenging areas in neurosurgery. Successful treatment of this subgroup of aneurysms is dependent on the mastery of technical nuances that have been pioneered and advanced over the past 4 decades. Although both the traditional transsylvian and subtemporal approaches have distinct advantages, each is associated with significant limitations. In this article, the senior author shares his insights into a hybrid approach: the extended lateral transsylvian approach. This approach combines the assets of the two traditional approaches while eliminating their liabilities.

Spontaneous thrombosis of a residual arteriovenous malformation in eloquent cortex after surgery: case report.

OBJECTIVE AND IMPORTANCE: The presence of a residual arteriovenous malformation (AVM) on postoperative angiograms is typically an indication for prompt return to the operating room to complete resection, because of the risk of early hemorrhage. This approach, however, may involve risks of neurological deficits when the residual AVM is in eloquent cortex. We present a case of complete thrombosis of a residual AVM after surgery. This residual AVM tissue was located in eloquent cortex. Complete spontaneous thrombosis of residual AVMs after surgery has only rarely been reported. This phenomenon raises questions regarding the most appropriate management for residual AVMs in eloquent cortex. CLINICAL PRESENTATION: The patient was a 43-year-old, right-handed, male patient with an AVM centered in the left precentral gyrus. The patient presented with medically intractable seizures and progressive right hemiparesis. After AVM resection, angiography revealed a residual AVM with early venous drainage. Angiography performed 1 week later demonstrated a persisting AVM nidus without early venous drainage. Angiography performed 3 months later demonstrated complete thrombosis of the residual AVM. INTERVENTION: The patient has been monitored for more than 1 year, without additional symptoms or therapy. CONCLUSION: We continue to advocate prompt return to the operating room when postoperative angiography reveals a residual AVM with persistent shunting. When the residual AVM is in eloquent cortex and is small, with a single draining vein, however, observation of the patient (with strict blood pressure control) and repeat angiography after 1 week represent an alternative strategy that is supported by this case report. As this case demonstrates, it is possible for small residual AVMs to thrombose. This may avert the need for reoperation for residual AVMs in eloquent cortex, with the potential for neurological deficits.

Trapping and revascularization for a dissecting aneurysm of the proximal posteroinferior cerebellar artery: technical case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Subarachnoid hemorrhage caused by an isolated dissection of the proximal portion of the posteroinferior cerebellar artery (PICA) is a rare problem. The optimal treatment to use for patients presenting with this clinical scenario varies and therefore is controversial in the literature. We report a patient in whom this problem was treated effectively with trapping of the diseased segment and revascularization of the PICA. We report this case to review this rare topic and to present our perspective on the indications for and the effectiveness of trapping and revascularization for proximal PICA dissections that cause hemorrhage. CLINICAL PRESENTATION: A 55-year-old man was transferred to our institution and admitted for Hunt and Hess Grade IV subarachnoid hemorrhage, which improved to Hunt and Hess Grade III after ventricular drainage. Imaging revealed the source of the hemorrhage to be a pseudoaneurysm related to the dissection of the proximal portion of the PICA. INTERVENTION: Three days after the initial bleeding episode, we operated on the patient. After the occipital artery was prepared for bypass, the diseased segment was trapped. The occipital artery-to-PICA anastomosis was then immediately performed distal to the trapped segment. CONCLUSION: On the basis of our experience, the literature regarding this topic, and the anatomy of the perforators of the PICA, we think that the best treatment for a pseudoaneurysm located within the first three segments of the PICA is trapping of the diseased segment followed by revascularization distal to the trapped segment. This approach should prevent rehemorrhage and should avoid iatrogenic ischemic complications of the brainstem.

Arterial reconstruction by direct surgical clipping of a basilar artery dissecting aneurysm after failed vertebral artery occlusion: technical case report and literature review.

OBJECTIVE AND IMPORTANCE: Dissecting aneurysms of the basilar artery are rare lesions with significant morbidity and mortality. Their management is controversial and often difficult. Although the rebleeding rate is high, clip reconstruction carries prohibitive risk because of the damage to the parent vessel induced by the dissection and the lack of tissue to gather. An enlarging pseudoaneurysm in the chronic phase, however, may have sufficient tissue for clip reconstruction. We present a case in which this strategy was used successfully. CLINICAL PRESENTATION: A 45-year-old woman presented 3 months after an initial presentation with a subarachnoid hemorrhage from a dissecting aneurysm of the basilar trunk at an outside institution. The aneurysm had grown compared with previous angiograms. INTERVENTION: The dominant vertebral artery was sacrificed. Despite this, the aneurysm continued to enlarge. Given the progressive enlargement of the aneurysm, the decision was made to proceed with arterial reconstruction by direct surgical clipping of the saccular component of the dissecting aneurysm. The patient made an excellent recovery with a durable result. CONCLUSION: Although clipping an intracranial pseudoaneurysm in the acute phase may carry a prohibitive risk, clipping such an aneurysm in the chronic phase may occasionally be warranted. To our knowledge, this is the first case reported in the literature in which direct surgical clipping was used as the primary mode of treatment for a basilar artery dissecting aneurysm that enlarged despite occlusion of the dominant vertebral artery. We review the literature on this rare pathological entity and discuss our management strategy.

Surgical management of a ruptured posterior choroidal intraventricular aneurysm associated with moyamoya disease using frameless stereotaxy: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: Prevention of rebleeding is the most important aspect of the management of hemorrhagic moyamoya disease, because rebleeding causes significant morbidity and mortality. CLINICAL PRESENTATION: A 26-year-old male patient with a history of moyamoya disease since the age of 3 years and multiple strokes was in a semicomatose state at presentation. He was found to have intraventricular and periventricular hemorrhages abutting the atrium of the right ventricle. His hospital course was complicated by a second hemorrhage. Both bleeding events were believed to be secondary to a ruptured right lateral posterior choroidal aneurysm. INTERVENTION: The aneurysm was excised and revealed histopathology consistent with a true saccular aneurysm. Frameless stereotactic guidance was used during surgery to minimize damage to collateral vessels and to shorten the surgical corridor. CONCLUSION: The management of hemorrhagic moyamoya disease should be modified based on the source of hemorrhage and its relation to a specifically located aneurysm. In the case of aneurysms arising from the choroidal artery, the general belief is that most of these represent pseudoaneurysms and have a tendency to regress spontaneously. Because of the rebleeding risk, we recommend early intervention in treating ruptured intracranial aneurysms using the least invasive surgical techniques.

Surgical management of unruptured posterior carotid artery wall aneurysms.

Intracranial aneurysms arising from the posterior wall of the supraclinoid carotid artery are extremely common lesions. The aneurysm dilation typically occurs in immediate proximity to the origin of the posterior communicating artery and, less commonly, the anterior choroidal artery (AChA). Because of the increasingly widespread use of noninvasive neuroimaging methods to evaluate patients believed to harbor cerebral lesions, many of these carotid artery aneurysms are now documented in their unruptured state, prior to occurrence of subarachnoid hemorrhage. Based on these factors, the management of unruptured posterior carotid artery (PCA) wall aneurysms is an important element of any neurosurgical practice. Despite impressive recent advances in endovascular therapy, the placement of microsurgical clips to exclude aneurysms with preservation of all afferent and efferent vasculature remains the most efficacious and durable therapy. To date, an optimal outcome is only achieved when the neurosurgeon is able to combine systematic preoperative neurovascular assessment with meticulous operative technique. In this report, the authors review their surgical approach to PCA wall aneurysms, which is greatly based on the extensive neurovascular experience of the senior author. Focus is placed on their methods of preoperative evaluation and operative technique, with emphasis on neurovascular anatomy and the significance of oculomotor nerve compression. They conclude by discussing surgery-related complications, with a particular focus on intraoperative rupture of aneurysms and their management, and the postoperative ischemic AChA syndrome.

A national fundamentals curriculum for neurosurgery PGY1 residents: the 2010 Society of Neurological Surgeons boot camp courses.

BACKGROUND: In July 2009, the Accreditation Council for Graduate Medical Education (ACGME) incorporated postgraduate year 1 (PGY1 intern) level training into all U.S. neurosurgery residency programs. OBJECTIVE: To provide a fundamentals curriculum for all incoming neurosurgery PGY1 residents in ACGME-accredited programs, including skills, knowledge, and attitudes that promote quality, patient safety, and professionalism. METHODS: The Society of Neurological Surgeons organized 6 regional "boot camp" courses for incoming neurosurgery PGY1 residents in July 2010 that consisted of 9 lectures on clinical and nonclinical competencies plus 10 procedural and 6 surgical skills stations. Resident and faculty participants were surveyed to assess knowledge and course effectiveness. RESULTS: A total of 186 of 197 U.S. neurosurgical PGY1 residents (94%) and 75 neurosurgical faculty from 36 of 99 programs (36%) participated in the inaugural boot camp courses. All residents and 83% of faculty participants completed course surveys. All resident and faculty respondents thought that the boot camp courses fulfilled their purpose and objectives and imparted skills and knowledge that would improve patient care. PGY1 residents' knowledge of information taught in the courses improved significantly in postcourse testing (P < .0001). Residents and faculty particularly valued simulated and other hands-on skills training. CONCLUSION: Regional organization facilitated an unprecedented degree of participation in a national fundamental skills program for entering neurosurgery residents. One hundred percent of resident and faculty respondents positively reviewed the courses. The boot camp courses may provide a model for enhanced learning, professionalism, and safety at the inception of training in other procedural specialties.